A mouse model of human oral-esophageal cancer

AUTOR(ES)

Opitz, Oliver G.

FONTE

American Society for Clinical Investigation

RESUMO

Squamous cancers of the oral cavity and esophagus are common worldwide, but no good genetically based animal model exists. A number of environmental factors as well as genetic alterations have been identified in these cancers, yet the specific combination of genetic events required for cancer progression remains unknown. The Epstein-Barr virus ED-L2 promoter (L2) can be used to target genes in a specific fashion to the oral-esophageal squamous epithelium. To that end, we generated L2–cyclin D1 (L2D1+) mice and crossbred these with p53-deficient mice. Whereas L2D1+ mice exhibit a histologic phenotype of oral-esophageal dysplasia, the combination of cyclin D1 expression and p53 deficiency results in invasive oral-esophageal cancer. The development of the precancerous lesions was significantly reversed by the application of sulindac in the drinking water of the L2D1+/p53+/– mice. Furthermore, cell lines derived from oral epithelia of L2D1+/p53+/– and L2D1+/p53–/– mice, but not control mice, formed tumors in athymic nude mice. These data demonstrate that L2D1+/p53+/– mice provide a well-defined, novel, and faithful model of oral-esophageal cancer, which allows for the testing of novel chemopreventive, diagnostic, and therapeutic approaches.

Documentos Relacionados

• Effect of LPS on the Viability and Proliferation of Human Oral and Esophageal Cancer Cell Lines
• Erratum: Effect of LPS on the Viability and Proliferation of Human Oral and Esophageal Cancer Cell Lines
• Erratum: Effect of LPS on the Viability and Proliferation of Human Oral and Esophageal Cancer Cell Lines
• A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens.
• Frequent mutation of the p53 gene in human esophageal cancer.